This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human brains have unique functional capacities, but how the human brain differs structurally and biochemically from that of other primates is poorly understood. We are pursuing these questions by identifying differences in gene and protein expression between species (humans, chimpanzees, and macaque monkeys), between brain regions (multiple cortical and subcortical sites), and between hemispheres. Gene-expression differences are determined using unfixed tissue samples from short post-mortem time (8 hours or less) cases. Samples are flash-frozen and stored at [unreadable]70[unreadable]80[unreadable]C. Messenger RNA is later extracted and hybridized to oligonucleotide microarrays to determining gene-expression levels for each sample. Possible species differences and regional differences are flagged by comparing microarray results across samples, and then are corroborated using quantitative real-time RT-PCR. Differences in levels of protein expression are determined by Western blotting. Finally, mRNA and protein are localized in cortical tissue using in situ hybridization and immunocytochemistry.